The Zuni Pueblo, located in New Mexico, has a population of 11,500. This small, isolated population has been relatively endogamous for several hundred years. The prevalence of end-stage renal disease at Zuni is 11- and 4- fold higher the U.S. White and composite American Indian rates, respectively. The prevalence of non-insulin-dependent diabetes mellitus is high among the Zuni and the epidemic is attributable mainly to diabetic nephropathy. Almost everyone at Zuni has a relative with ESRD, leading to strong community support for renal research. In response to this need we established the Zuni Kidney Project which is conducting a population-based survey of all Zuni residents greater than or equal to 5 years of age. We are ascertaining family structure and quantifying glycemic control, proteinuria, and renal function in all participants. The present project will establish a DNA repository and identify genome segments and environmental-genetic interactions that modulate the risk for the onset and/or progression of diabetic nephropathy and intermediate phenotypes. Our investigative team includes representatives from the Zuni Pueblo, University of New Mexico Health Sciences Center, Indian Health Service, Southwest Foundation for Biomedical Research, Phoenix office of NIDDK, Strong Heart Study, University of Pennsylvania, and the Istituto Scientifico H San Raffaele. This collaborative approach allows us to directly compare results obtained in the Zuni with those in Pima Indians and Strong Heart Study participants. Results obtained in these Native American populations will be compared with those in other ethnic groups studied by the remaining participating investigating centers.